The secretory immune system of the eye is designed to protect the ocular surface against microbial invasion. This system, by acting primarily through secretory IgA (sIgA) antibodies, prevents bacterial colonization, inhibits viral adhesion, abolishes parasitic infestation and blocks toxin-induced damage in mucosal epithelial cells. Thus, sIgA may play a unique and crucial role in preserving corneal integrity and defending against severe visual impairment and possible blindness. The long-range objective of this grant application is to advance our understanding of how the neural-endocrine system regulates the secretory immune system of the eye. Experimental procedures involve rat and mouse models, cell cultures, flow cytometry, autoradiography, sIgA transport studies, ligand binding determinations, immunoassays, chromatographic techniques, immunofluorescence and electron microscopy, image analysis, immune response studies with defined soluble, particulate and viral antigens, autoimmune disorders and endocrine organ ablation and reconstitution studies. Specific aims are: (1) To identify the hormonal and neuroendocrine factors that regulate lacrimal gland immunity, structure and function. These studies include (a) determination of the endocrine interactions controlling the expression, secretion and function of secretory component (SC) in lacrimal gland acinar cells in vitro; SC is a critical determinant for surface defense and modulates the transport of IgA antibodies in tears. (b) evaluation of the neural-endocrine interrelationships governing the secretory immune system of the eye in vivo. These latter experiments will also identify the hormonal and neuroendocrine factors regulating lacrimal gland morphology and tear production. (2) To analyze the neural-endocrine impact on the ocular secretory immune response to defined soluble, particulate and viral antigens. (3) To develop an endocrine strategy to ameliorate or prevent specific autoimmune disorders of the lacrimal gland. Results from these studies should clarify the extensive and complex interactions between the neural, endocrine and immune systems in the lacrimal gland. In addition, findings may have health relatedness for the eye, because they (a) explore the neural and endocrine mechanisms regulating the ocular secretory immune response to antigenic challenge; (b) examine a possible hormonal strategy to effectively treat specific autoimmune disorders of the lacrimal gland and (c) evaluate hormonal and neural factors that modulate lacrimal gland structure and tear production.